The goal of this project is to develop new diagnostic technology for detection and molecular analysis of cancer cells, especially circulating tumor cells. Our approach will be based on the previously developed DMR (diagnostic magnetic resonance) system that combines a miniaturized NMR probe with targeted magnetic nanoparticles for detection and molecular profiling of cancer cells. The system measures the transverse relaxation rate of water molecules in biological samples in which target cells of interest are labeled with magnetic nanoparticles. In preliminary study, we have detected a few cancer cells in fine needle aspirates, profiled the expression of cellular markers, and measured the pathway inhibition in small numbers of cancer cells. To further advance the DMR technology for molecular and cellular sensing of CTC, we propose three aims: 1) we will synthesize and further develop a new class of magnetic nanoparticles with high magnetic moments and optimize their chemical, biological properties for CTC labeling;2) we will implement a new DMR chip that can separate CTC from whole blood, measure multiple cancer markers in parallel, and sense the magnetic moments of individual cancer cells; 3) we will evaluate the clinical utility of the developed system using human samples, particularly detecting cancers outlined in the RFA (e.g. ovarian cancer, pancreatic cancer, glioma). Technology, materials and processes developed and optimized in this project will also be useful for Project 4 (implantable NMR based sensors), Projects 1 and 2 (targeting cancer cell populations) and Project 5 (novel hybrid nanomaterials).